The Principal Investigator and coinvestigators from the Department of Biological Chemistry and Molecular Pharmacology and Molecular Genetics at the Harvard Medical School and from the Department of Medicine at Massachusetts General Hospital request funds for a 500MHz NMR Spectrophotometer to conduct research into the structure and function of proteins and polypeptides. Specific research problems address proteins in mercury detoxification, (merR, A,B, gene products), microcins as antibacterial proteins, amylogenins, Ca++-sequestering proteins in bone enamel, the role of key active site residues in the ADO-Pribosylating toxins, diptheria toxin and P. aeruginosa exotoxin-A, the nature of the DNA binding domains conned transcriptional activation domains in the yeast transcriptional activating protein GCN-4, and structure-function studies in insulin folding. Strong expertise in site-directed and selective mutagenesis coupled with experience in overproduction or proteins or protein fragments in quantity by high field NMR methods.